This application requests funds for the purchase of a Nordion Gammacell 40 Low Dose Research Irradiator for use by investigators at Cold Spring Harbor Laboratory. The gamma irradiator will be used by multiple Cold Spring Harbor Laboratory (CSHL) investigators for a variety of research purposes, most of which exploit the ability of gamma radiation to induce double-stranded DNA breaks at lethal and sublethal doses, both in tissue culture cells and in whole organisms. One major use is for specialized applications in animal models, including experiments to improve success of bone marrow transplantation, to identify and characterize genes involved in cancer, and to test the efficacy of radiation and chemotherapeutic drugs in anti-cancer therapy. The irradiator is also used extensively and is required for generating mitotically inactive cells for use as feeder layers in gene targeting experiments, and for the study of the basic biology of biochemical pathways of DNA damage repair. In the past, a gamma irradiator has been crucial for some of the most cutting edge advances at the Laboratory, including: (i) studies examining p53 effector functions in lymphomagenesis; (ii) studies to generate new mouse models of various hematopoietic malignancies; (iii) studies identifying the mIR17-92 microRNA cluster as the first non-coding RNA that contributes to tumorigenesis and a bona fide human oncogene; (iv) studies documenting the ability of NO inhibitors to expand hematopoietic stem cells, and (v) studies on the role of bone marrow derived stem cells in angiogenesis. The Nordion irradiator is requested because CSHL has expanded its animal research such that the majority of its animal colonies are located at an off-site facility, and it is no longer feasible to accommodate all of the research involving animal irradiation on site. A new Nordion Gammacell 40 irradiator will greatly facilitate the research at the Laboratory and is important for it to remain competitive in various areas biomedical research. [unreadable] [unreadable] [unreadable]